Streptococcus pneumonia is one of the most common invasive bacterial pathogens in children. The increase( incidence of pneumococcal diseases has been complicated by the appearance of multidrug resistant isolates, low levels of serotype-specific antibodies in young children and the absence of routine, effective immunization. Understanding the mechanisms of acquisition and spread of multidrug resistant microorganisms and their interaction with the immune system during colonization and invasion in order to design novel approaches for therapy of these infections is the long term career goal of this candidate. In the sponsor's laboratory the applicant has been studying the molecular epidemiology of penicillin resistant, pediatric isolates of S. pneumonia. Results of these studies have lead to the hypothesis that multidrug resistant defenses through capsular transformation. The proposed project would involve creating mutants in the genes for the capsular of S. Pneumonia and clarifying the mechanisms by which capsular transformation occurs in vivo. Information about this process improve our understanding of the strategies pneumococci have developed for colonization and infection and the essential criteria for successful immunization and therapy.